He drew her back to him, and she yielded and settled closely in the curve of his arm, and he told her the story. New Word List Word List. Save This Word! We could talk until we're blue in the face about this quiz on words for the color "blue," but we think you should take the quiz and find out if you're a whiz at these colorful terms. Downloadable Version. Advanced Filter. Web Service. OECD Statistics. No limit on publication year was imposed. First, the literature identified through the electronic search was primarily assessed for eligibility by inspecting the titles and abstracts.
We decided to divide the literature between three reviewers because of the large number of hits. Two additional reviewers were appointed to ensure the quality of the first screening process.
In the second step, the full texts of the qualified studies were retrieved and critically evaluated for their final inclusion in the data collection process. The three reviewers independently assessed the articles for eligibility, and any discrepancies were resolved by discussions and when necessary, by adjudication from another reviewer.
Thirteen authors of the selected studies were contacted for additional data on physical activity. The tool includes seven domains that lead to the risk of bias.
These domains are due to 1 confounding, 2 selection of participants, 3 exposure assessment, 4 misclassification during follow-up, 5 missing data, 6 measurement of the outcome, and 7 selective reporting of results. The domains 1, 2 and 3 are directly considered in rating the certainty of evidence. The included studies were independently evaluated by two assessors EM, LM. Any inconsistencies in the evaluations were documented and then discussed with a third member of the research team WG and resolved by mutual agreement.
We pooled aggregated data using the random effects meta-regression model, as suggested by DerSimonian and Laird [ 16 ], assuming random variance of the true effect of physical activity among studies, especially due to diversity in assessment methods. For studies that reported results from one cohort in stratified estimates e. If information was missing, the distributions of cases and person-years were estimated using the total number of cases and the total number of participants plus the follow-up period, as previously described [ 19 ].
If the lowest category was not used as a reference, the reported risk estimates were recalculated using Orsini et al. If a study reported the exposure categories as ranges, then for each category, the midpoint between the lower and upper limit was calculated. For open categories, we assumed that the width was the same as the adjacent category.
A potential non-linear association was evaluated using a restricted cubic spline model with three knots at the 10th, 50th and 90th percentile of frequency of the exposure [ 18 ].
The indication of nonlinearity was tested using a likelihood ratio test. The heterogeneity was described using the measure of inconsistency I 2 , and tau 2 was used to measure the variance between the included studies [ 21 ].
Subgroup analysis and meta-regression were performed to explore the heterogeneity across studies. One reviewer assessed the certainty of evidence and a second reviewer revised the certainty assessments as necessary. Due to the inherent limitations in observational studies, certainty of evidence starts at low and can be further downgraded based on risk of bias, imprecision, inconsistency of results, indirectness of evidence and publication bias or upgraded based on large magnitude of effect, a dose-response gradient, or opposing residual confounding [ 26 ].
Following the GRADE recommendations for informative statements to communicate the findings we developed summary of findings tables and included plain language summaries based on effect magnitude and certainty of evidence in the result section [ 27 ]. The systematic database search yielded 44, publications in total. Three additional studies were identified from the reference lists.
Full texts were retrieved and screened for articles with the potential for inclusion. Studies with ineligible exposure did not directly measure the physical activity but another facet of movement behaviour mostly sedentary time; b.
The 28 included studies were all published during the past two decades and based in numerous countries throughout the world. Out of these, 25 studies were prospective cohort studies, 2 prospective follow-ups to case-control studies and 3 follow-up studies of RCTs [ 13 , 28 , 29 ]. The sample sizes varied considerably from [ 30 ] to 15, [ 31 ], with a total of 27, participants diagnosed with breast cancer, 32, with T2D, with COPD and 42, with IHD.
The follow-up duration ranged from 3. A summary of the main characteristics of the cohorts is displayed in Table 1. All-cause mortality was reported as the primary outcome in all included studies.
Other reported outcomes were breast cancer mortality, recurrence and new primary events, cardiovascular disease mortality, IHD mortality and respiratory mortality. All exposure assessments of post-diagnosis physical activity were based on self- or interviewer-administered questionnaires.
The time from diagnosis to physical activity measurement varied from three to 6 months post-diagnosis [ 48 ]. The longest follow-up was 14 years [ 53 ]. Detailed information on the measurement instruments for physical activity assessment can be found in Supplementary file 3. From the 28 publications assessed, eleven were evaluated to have a moderate risk of bias [ 13 , 28 , 30 , 32 , 35 , 37 , 46 , 48 , 49 , 50 , 53 ], and the remaining studies had a serious risk of bias.
The main domains that introduced bias were 1 the confounding domain mainly due to the lack of adjusting for potential confounders such as the level of physical activity before diagnosis and 2 the domain of deviations from intended interventions. This point refers to the uncertainty as to whether the physical activity exposure measured at a given time in the observational studies is representative for the habitual activity levels of the individuals.
It is important to note that all studies used validated measurement instruments see Supplementary file 3 but due to the assessment of physical activity based on self-reports, a potential misclassification of physical activity could not be excluded.
The risk of bias for each domain in the 28 studies is shown in Fig. In addition, Table 1 contains the final risk of bias evaluation across the studies, and Supplementary file 4 includes the detailed results of the risk of bias assessment. The overall certainty of evidence for the reduction of all-cause mortality germane to post-diagnosis physical activity is presented in Table 2.
The results of the linear dose—response meta-analyses are presented in Fig. Linear dose—response meta-analysis for the association between post-diagnosis physical activity and all-cause mortality. The subgroup analysis for breast cancer Supplementary file 7 , Table S7. Asymmetry was represented by the lack of small studies with null findings. Figure 4 presents the non-linear dose—response meta-analysis among the four NCD populations.
Non-linear dose—response meta-analysis for the association between post-diagnosis physical activity and all-cause mortality. After this, the curves flatten out. In this systematic review and meta-analysis, higher levels of post-diagnosis physical activity were associated with a reduction in all-cause mortality in adults with breast cancer, T2D, IHD and COPD. Our dose—response meta-analysis highlights a non-linear association between physical activity levels and mortality characterized by 1 no threshold for the beneficial effect of physical activity on mortality i.
Higher post-diagnosis physical activity levels may result in a slight reduction of all-cause mortality in breast cancer, T2D and IHD. The evidence is very uncertain about this effect in individuals with COPD. However, the unbalanced distribution of studies and the low overall number of studies for some subgroups make the interpretation difficult. Hence, it is uncertain whether the length of follow-up can explain the heterogeneity in the effect size. Due to a lack of studies, we were not able to determine dose—response relationships for physical activity and mortality in adults with low back pain, osteoarthritis, depressive disorder, lung cancer or stroke.
Our findings confirm previous reviews and linear meta-analyses, which showed a general correlation between higher physical activity levels and lower mortality rates in adults with T2D [ 6 ] and breast cancer [ 7 , 55 , 56 ]. For women with breast cancer, the one available randomized controlled trial reported HR for mortality from 0.
However, since no specific activity levels are measured in this study, HRs are difficult to compare with the HR per each ten metabolic equivalent tasks hours calculated by us. Findings may differ because of the differences in a the outcome measured all-cause mortality vs.
Our applied non-linear dose—response-analysis extends and refines these previous linear analyses. The associations between different post-diagnosis physical activity levels and mortality for adults with NCDs are very similar to those recently developed for the general population [ 9 , 58 , 59 ].
Therefore, our results confirm the following main characteristics of the dose—response curves in the general population for adults with selected NCDs: 1 no threshold for the positive effect, 2 the most pronounced SHR reductions occurs between adults with little physical activity compared to those being physically inactive, and 3 no negative effects on mortality at higher volumes of physical activity.
Ekelund et al. In our study, higher physical activity levels were associated with continuously small declines in mortality rates for IHD and T2D. No data is available on higher physical activity levels for COPD. Although one study reported data on stroke patients [ 52 ], it was not sufficient to be included in the meta-analysis. For 4 NCDs low back pain, osteoarthritis, depressive disorder, lung cancer , we were not able to find appropriate studies for our analysis.
Thus, our findings confirm the research gap in the clinical populations already identified before [ 9 ]. Our study has several strengths. Its main strength is the broad and comprehensive systematic literature search for 9 NCDs that have a high relevance for public health.
For the first time, our work generates a broad overview of post-diagnosis physical activity and mortality for adults with NCDs. Another strength is the applied non-linear dose—response meta-analysis that enables precise statements regarding the effective dose of physical activity for reduced mortality rates.
This information helps with the adaption or development of exercise recommendations for adults with NCDs. In addition, the use of the new ROBINS-I tool is a methodological strength that allows for a precise estimation of the risk of bias in different domains e.
Despite its strengths, this systematic review and meta-analysis has limitations that should be acknowledged. First, at the outcome level of the study, the risk of bias in the measurement of physical activity in the original studies is unknown.
All studies measured physical activity levels using self-reports. If the over-reporting of physical activity already plays a role at low physical activity levels, the actual high relative reduction in mortality rates of somewhat physically active persons compared to inactive persons could be underestimated. Most of the studies have measured the level of physical activity only at one point in time, thus meaning that no information on changes over time is available.
This might lower the accuracy of the dose—response curves. Readers must therefore always check the product information and clinical procedures with the most up to date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations.
The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breastfeeding. The dose—response relationship is the measurement of the relationship between the dose of a substance administered and its overall effect the response , either therapeutic or toxic.
The dose—response relationship is based on observed data from experimental animal, human clinical, or cell studies. Generally, the higher the dose, the greater the response Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.
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